[11C]PIB PET Is Associated with the Brain Biopsy Amyloid-β Load in Subjects Examined for Normal Pressure Hydrocephalus

• Published in: Journal of Alzheimer's disease Vol. 67; no. 4; p. 1343
• Main Authors: Rinne, Juha O, Suotunen, Timo, Rummukainen, Jaana, Herukka, Sanna-Kaisa, Nerg, Ossi, Koivisto, Anne M, Rauramaa, Tuomas, Någren, Kjell, Hiltunen, Mikko, Alafuzoff, Irina, Rinne, Jaakko, Jääskeläinen, Juha E, Soininen, Hilkka, Leinonen, Ville
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2019
• Subjects: Aged; Biopsy - methods; Carbon Radioisotopes - pharmacology; Female; Finland; Follow-Up Studies; Frontal Lobe - diagnostic imaging; Frontal Lobe - metabolism; Frontal Lobe - pathology; Humans; Hydrocephalus, Normal Pressure - diagnosis; Hydrocephalus, Normal Pressure - metabolism; Hydrocephalus, Normal Pressure - pathology; Hydrocephalus, Normal Pressure - psychology; Male; Mental Status and Dementia Tests; Positron-Emission Tomography - methods; Reproducibility of Results; tau Proteins - metabolism; Ventricular Pressure; Ventriculoperitoneal Shunt - methods; Finland; Amyloid, brain biopsy, cerebrospinal fluid, normal pressure hydrocephalus, positron emission tomography
• DOI: 10.3233/JAD-180645

Idiopathic normal pressure hydrocephalus (iNPH) is frequently associated with concomitant amyloid-β (Aβ) pathology. To compare the [11C]PIB PET uptake in the patients with suspected iNPH to Aβ and hyperphosphorylated-tau (HPτ) in the right frontal cortical biopsy, the cerebrospinal fluid (CSF) Aβ, the response to a CSF shunt, and the final clinical diagnosis of Alzheimer's disease (AD). Patients (n = 21) from Kuopio NPH Registry (http://www.uef.fi/nph) with intraventricular pressure monitoring, immunostaining for Aβ and HPτ in the right frontal cortical biopsies, and a Mini-Mental State Examination and a Clinical Dementia Rating underwent [11C]PIB PET. Aβ, total tau, and Pτ181 were measured by ELISA from the ventricular (n = 15) and the lumbar (n = 9) CSF. Response to the shunt was seen in 13 out of the 15 shunted patients. AD was diagnosed in 8 patients during a median follow-up of 6 years (mean 7.3±2.4 years, range 3-1). [11C]PIB uptake in the right frontal cortex (ρ= 0.60, p < 0.01) and the combined neocortical [11C]PIB uptake score (ρ= 0.61, p < 0.01) were associated with a higher Aβ load in the right frontal cortical biopsy. Excluding one (1/15) outlier, [11C]PIB uptake was also associated with the ventricular CSF Aβ (ρ= -0.58, p = 0.03). The findings show that [11C]PIB PET can reliably detect simultaneous amyloid pathology among the iNPH patients. Further studies will show whether amyloid PET could predict a clinical response to the shunt operation. In addition, the presence of Aβ pathology in the patients with iNPH might also warrant treatment with current AD drugs.